Welcome
to the latest edition of Vaccines for the Future. This issue
highlights several new milestones for our program, including the launch of
two clinical trials and the addition of several new partnerships. A Phase 1
trial for an enterotoxigenic Escherichia coli vaccine candidate began
in June, while Africa’s largest influenza vaccine trial was launched in May.
We have also added new partnerships to our pneumococcal and influenza vaccine
development projects. In addition, we share the launch of the inaugural
Advance Market Commitment, which is focused on increasing access to vaccines
against pneumococcal disease.

Finally,
we feature several new resources, including a PATH report and Call to Action
on diarrheal disease and exciting additions to the Vaccine Resource Library.
We also share a journal article on cholera in Africa to which members of our
staff contributed. As always, we hope these updates continue to be useful,
and we welcome your feedback.

PATH supported the June
launch of a Phase 1 clinical trial of an oral enterotoxigenic Escherichia
coli (ETEC) vaccine candidate with partner ACE BioSciences, a vaccine
company based in Denmark. The trial, which is taking place in Baltimore, Maryland, at the Center for Immunization Research at Johns Hopkins University, will test the safety and immunogenicity of ACE527, a live attenuated, whole
cell vaccine which is comprised of three ETEC strains and should provide
broad coverage. Researchers are enrolling 36 healthy adult volunteers in the
study and will administer two vaccine candidate doses to each participant,
either at a high or low dose level. The trial is expected to be completed by
September 2009 with results available by December 2009.

PATH’s enteric vaccine
development project also supported the recent Good Manufacturing
Practices production of double mutant heat-labile toxin (dmLT) adjuvant at
the Walter
Reed Army Institute of Research’s Pilot Bioproduction Facility in Silver Spring, Maryland. The dmLT, a highly promising new adjuvant that PATH in-licensed
from Tulane University, is also an ETEC antigen that may offer protection
against disease. The newly produced vials of dmLT will next go through lot
release tests, and then a formal Good Laboratory Practices toxicity study
later this year. All of these efforts are in preparation for a planned Phase
1 clinical trial of dmLT, expected to begin in 2010.

As part of its influenza vaccine
project, PATH recently entered into two new research collaborations to
support its strategy of increasing developing world access to affordable
influenza vaccines. In the first partnership, the Midwest
Research Institute of Kansas City, Missouri, will serve as the primary
preclinical facility performing immunogenicity, challenge, and toxicology
studies, as well as associated assays for PATH’s influenza vaccine partners.
The second collaboration teams PATH with Neugenesis
Corporation (PDF) of Burlingame, California, to conduct feasibility
studies on an influenza vaccine production system from the transformed
filamentous fungus Neurosporacrassa, which can be used to make
virus-like particles.

Africa’s
largest influenza vaccine trial to date launched by PATH and partners

PATH’s vaccine development
program, in collaboration with the Institut de Recherche pour le
Développement and the Institut Pasteur de Dakar, recently launched
a large-scale,
cluster-randomized trial funded by the US
Centers for Disease Control and Prevention to evaluate the
effectiveness of inactivated influenza vaccine among children in Senegal. In
May and June, nearly 8,000 children six months to ten years of age in the Fatick District of Senegal were enrolled and vaccinated as part of the study, making it the
largest influenza vaccine trial ever conducted in Africa. Enrolled children
received either a licensed trivalent influenza vaccine or a beneficial
control vaccine—inactivated polio vaccine.

In the upcoming
months, investigators will conduct passive and active surveillance to identify influenza among participants and in their
communities. In addition to evaluating the protection afforded to vaccinated
children, investigators will evaluate the extent to
which immunizing only children, the suspected main transmitters of influenza,
effectively reduces disease in the rest of the community. Such information
will help national and global public health officials understand how to
most appropriately use influenza vaccines in Africa. By utilizing active
surveillance in a demographically well-defined population, the study will
also enable the calculation of influenza rates to help define the burden of
influenza, something almost totally unknown in tropical regions of Africa, as
well as help strengthen Senegal’s already exemplary national influenza surveillance program.

PATH’s pneumococcal
vaccine project recently signed separate agreements with vaccine
producers Serum Institute of India Ltd. and China National Biotec
Group’s Chengdu Institute of Biological Products to speed the development
of affordable pneumococcal conjugate vaccines (PCVs) against Streptococcus
pneumoniae that are optimal for use in low-resource countries. PCVs
couple the polysaccharide capsule of pneumococcal serotypes with carrier
proteins to make them immunogenic in infants and toddlers. These PCVs will
target the seven or eight strains most prevalent in Asia and Africa, which cause more than 60 percent of invasive disease in children under five years
old. By producing vaccines in India and China, PATH aims to reduce
manufacturing costs to ultimately meet technical and pricing requirements for
Advance Market Commitments through the GAVI Alliance and World Bank. The
strategy is to combine proven conjugation methods with new technologies for
rapid and cost-effective vaccine development. To support the China work, PATH is also partnering with South Africa’s Biovac Institute to provide technical
expertise.

In June, global
health partners announced the launch of the first-ever Advance
Market Commitment (AMC), which will speed the
availability of vaccines against Streptococcus pneumoniae for 60 of
the world’s lowest-income countries by 2015. The initiative is an
important step toward reducing the traditional 15- to 20-year lag between the
introduction of new vaccines in wealthy countries and their availability in
the developing world. Sponsors estimate the effort
could help save the lives of more than seven million children from
pneumococcal disease by 2030. Under the AMC, donors commit funds to guarantee
the price of future vaccines, creating incentives for producers and
catalyzing competition on supplying vaccines at long-term lower prices. As a
result, low-resource countries will be able to access critical pneumococcal
vaccines for US$3.50 per dose instead of the current cost of US$70. Over the
next six years, the Bill & Melinda Gates Foundation and the governments
of Italy, the United Kingdom, Canada, Russia, and Norway are funding the AMC
pilot for a total of US$1.5 billion and the GAVI Alliance has committed
US$1.3 billion. Other key partners include the World Bank for fiduciary
support, UNICEF for vaccine procurement and distribution, and the World
Health Organization for ensuring that all pneumococcal vaccines developed
through an AMC comply with technical standards.

PATH supported the recent
production of clinical trial lots of the RV3 rotavirus vaccine candidate,
which is being developed by Murdoch Childrens Research Institute (MCRI) in Australia. MCRI contracted Meridian
Life Science, Inc. in Memphis, Tennessee, to manufacture the candidate
according to appropriate current Good Manufacturing Practices for their
upcoming Phase 1 and 2 clinical trials. The Phase 1 trial is expected to
begin in the fourth quarter of 2009 in Australia. PATH is also involved in
the development of RV3 through participation in its vaccine advisory
committee. Dr. Duncan Steele, a senior technical officer at PATH, is a member
of the RV3 vaccine advisory committee and chaired their most recent meeting
on June 30. Dr. Georges Thiry, director of PATH’s rotavirus vaccine
development project, also participated in the meeting as an observer. The
meeting was followed by a celebration to honor Dr. Ruth Bishop, who
discovered rotavirus in 1973, and featured remarks and presentations from
leading virologists and experts in the rotavirus field, including Dr. Steele.

In other news, PATH hosted its
3rd Annual Manufacturers Meeting for its partners developing the
bovine-human reassortant rotavirus vaccine (BRV) candidate. The meeting,
which was held in Bangkok, Thailand, on June 17 to 18, brought together all
of the manufacturers actively developing the BRV, as well as several
supporting organizations. This two-day meeting provided an opportunity to
discuss technical aspects of the development of the BRV candidate, including
quality-control assays, formulation and process development, clinical
evaluation, validation of assays, design of efficacy studies, and regulatory
issues.

In May, PATH released a new
report highlighting the deadly effects diarrheal diseases have on children in
the developing world and the lifesaving solutions to prevent and treat this
childhood killer. The report, Diarrheal Disease:
Solutions to Defeat a Global Killer, emphasizes the need to refocus
attention on diarrheal disease and the array of prevention and treatment
solutions that exist, including safe water, improved sanitation and hygiene,
vaccines, zinc treatment, and oral rehydration therapy/oral rehydration
solution. The report’s accompanying Call to Action unites
advocates from the health, development, environmental, water/sanitation, and
research communities to raise the visibility of diarrhea and solutions to
address it. These more than 90 organizations, such as the United Nations
Foundation, Save the Children, and WaterAid America, have joined together to reach
donors, international health policymakers, national leaders, and the private
sector to push for increased funding and political will to reduce death and
illness from diarrheal disease. With a coordinated effort, children do not
have to continue dying from this preventable illness.

An article published in the
May issue of the journal Science underscores the need for reevaluating
the use of cholera vaccines in Africa. Drs. Richard Walker, A. Louis
Bourgeois, and Duncan Steele of PATH contributed to the policy forum
article (subscription required), which describes the cholera crisis in Africa and the need for flexibility in prevention and treatment efforts. The article proposes
a new strategy for curbing the deadly cholera outbreaks that have been raging
across Africa for more than a decade. By combining the current use of oral
rehydration solution with a mass vaccination effort using cholera vaccines,
the number of deaths from this preventable disease could be dramatically
reduced.

Vaccines for
Enteric Diseases, Malaga, Spain, September 9 to 11. This conference brings together experts in
the fields of vaccines and enteric diseases and will address a variety
of issues around research, development, and evaluation of vaccines for
enteric infections. Participants will attend sessions on disease burden,
the state-of-the-field, and clinical trials, among other topics. In
addition to co-sponsoring the event, PATH’s Dr. Duncan Steele is serving
as chair of the conference and several PATH staff will present and
moderate sessions at the meeting.

Developing Country Vaccine Manufacturers
Network Annual Meeting, Beijing, China, September 14 to 18. This conference brings together vaccine
manufacturers from developing countries to exchange ideas and discuss
topics related to vaccine needs in low-resource countries. This year’s
conference, hosted by China National Biotec Group, will provide
participants with a forum for discussing topics related to disease
burden, vaccine research and development, regulatory approval, and more.
Dr. John Boslego, director of PATH’s vaccine development program, will
present on PATH’s work to accelerate the development of new vaccines for
populations in low-resource countries.

3rd Vaccine Global Congress,
Singapore, October 4 to 6. This annual conference, hosted by the journal Vaccine,
gives participants access to a state-of-the-art report on the
development of vaccines for infectious and non-infectious diseases. Participants
will hear from experts and opinion leaders in the field and network with
academics and researchers, regulatory and governmental agencies,
charities, and health and industry professionals.

44th US-Japan
Conference on Cholera and Other Bacterial Enteric Infections, San Diego, CA, October 12 to 14. Part of the
US-Japan Cooperative Medical Science Program, a joint cooperative
research effort in the medical sciences that concentrates on health
problems in Southeast Asia, this conference brings together leading
Japanese, American, and other experts in enteric diseases. Participants
will discuss the latest scientific advances in vaccines, epidemiology,
and research related to cholera and other bacterial enteric infections.

5th African
Rotavirus Symposium, Accra, Ghana, October 14 to 17. This symposium brings together diarrheal
disease experts to discuss rotavirus in Africa. The symposium, held in
conjunction with the 30th African Health Sciences Congress,
will include topics related to rotavirus disease burden and
surveillance, vaccine research and development, and clinical trials.

PATH’s vaccine
development program is working to accelerate the development of innovative,
safe, effective, and affordable vaccines against the leading causes of
childhood deaths in the developing world, pneumonia (pneumococcal disease)
and diarrheal disease (rotavirus, Shigella,
and enterotoxigenic Escherichia coli), as well as new influenza
vaccines for the global population. PATH is also partnering on vaccine
development through its Malaria Vaccine Initiative and the Meningitis Vaccine
Project. Additionally, PATH works to ensure the worldwide availability of
vaccines through its vaccine access and delivery program. The work of the
vaccine development program is currently supported by grants from the Bill
& Melinda Gates Foundation and the US Centers for Disease Control and
Prevention.

Learn
more about PATH’s work

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periodic email updates highlighting programmatic activities from throughout
the organization. Find out what we’re working on, where we’ll be presenting
our work, and what new publications and tools are available. Sign up for
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